Biology subjects

Sivakumar, K.

Publications and source records attributed to Sivakumar, K..

9 recordsLinked to original sources

bioRxiv2025

Ventral tegmental area dopamine controls timing variability

Precision defines successful behavior, yet the brain mechanisms promoting precision are unclear. Here, we dissect dopaminergic circuits controlling precision along a single behavioral dimension - the timing of action. We use an interval timing paradigm that requires participants to indicate their estimate of an interval of several seconds with a motor response. We find that humans with Parkinsons disease (PD) had increased timing variability that predicted PD-related cognitive deficits and executive dysfunction. Surprisingly, lesioning ventral tegmental area (VTA) dopamine neurons increased temporal variability. Further, GCaMP6s fiber photometry demonstrated that VTA dopamine neuron activity is strongly modulated at the start of temporal intervals, and that this trial start-related activity predicted temporal variability. Finally, we found that stimulation of VTA dopamine neurons improved timing by decreasing temporal variability in both intact and dopamine-depleted animals. Our data establish a model of cognitive symptoms of human PD and provide insight into the neuronal control of temporal variability, which impacts a wide range of executive functions.

neuroscience↗

bioRxiv2025

Timing, movement, and reward contributions to prefrontal and striatal ramping activity

Across species, prefrontal and striatal neurons exhibit time-dependent ramping activity, defined as a consistent monotonic change in firing rate across temporal intervals. However, it is unclear if ramping activity is related to the cognitive process of estimating time, or to other behavioral factors such as anticipating reward or regulating movements. Here, we harnessed two novel approaches to determine how these factors contribute to prefrontal and striatal ramping activity in mice performing an interval timing task. First, to determine how movement contributes to ramping activity, we tracked movement velocity using DeepLabCut as well as task-specific movements while recording prefrontal or striatal ensembles during interval timing. We found that time was more accurately decoded by ramping neurons than movement-modulated neurons, with the exception of prefrontal velocity-modulated neurons. Second, to disambiguate temporal signals from anticipatory reward signals we compared activity patterns in neurons that were recorded during interval timing to the same neurons recorded during a Pavlovian conditioning task. We found more ramping activity and more accurate temporal decoding by neuronal ensembles during interval timing compared to Pavlovian conditioning. Together, these data quantify contributions of time estimation, movement, and reward anticipation in prefrontal and striatal ensembles, and they suggest that ramping is a cognitive signal that estimates time. Our results provide insight into how prefrontal and striatal ensembles multiplex information to effect temporal control of action.

neuroscience↗

bioRxiv2024

Long-term, cell type-specific effects of prenatal stress on dorsal striatum and relevant behaviors in mice

Maternal stress during pregnancy, or prenatal stress, is a risk factor for neurodevelopmental disorders in offspring, including autism spectrum disorder (ASD). In ASD, dorsal striatum displays abnormalities correlating with symptom severity, but there is a gap in knowledge about dorsal striatal cellular and molecular mechanisms that may contribute. Using a mouse model, we investigated how prenatal stress impacted striatal-dependent behavior in adult offspring. We observed enhanced motor learning and earlier response times on an interval timing task, with accompanying changes in time-related medium spiny neuron (MSN) activity. We performed adult dorsal striatal single-cell RNA sequencing following prenatal stress which revealed differentially expressed genes (DEGs) in multiple cell types; downregulated DEGs were enriched for ribosome and translational pathways consistently in MSN subtypes, microglia, and somatostatin neurons. DEGs in MSN subtypes over-represented ASD risk genes and were enriched for synapse-related processes. These results provide insights into striatal alterations relevant to neurodevelopmental disorders.

neuroscience↗

bioRxiv2024

Amphetamine increases timing variability by degrading prefrontal ramping activity

BackgroundAmphetamine is a commonly abused psychostimulant that increases synaptic catecholamine levels and impairs executive functions. However, it is unknown how acute amphetamine affects brain areas involved in executive control, such as the prefrontal cortex. We studied this problem in mice using interval timing, which requires participants to estimate an interval of several seconds with a motor response. Rodent prefrontal cortex ensembles are required for interval timing. We tested the hypothesis that amphetamine disrupts interval timing by degrading prefrontal cortex temporal encoding. MethodsWe first quantified the effects of amphetamine on interval timing performance by conducting a meta-analysis of 11 prior rodent studies. We also implanted multielectrode recording arrays in the dorsomedial prefrontal cortex of 7 mice and then examined the effects of 1.5 mg/kg D-amphetamine injected intraperitoneally on interval timing behavior and prefrontal neuronal ensemble activity. ResultsA meta-analysis of previous literature revealed that amphetamine produces a large effect size on interval timing variability across studies but only a medium effect size on central tendencies of interval timing. We found a similar effect on interval timing variability in our task, which was accompanied by greater trial-to-trial variability in prefrontal ramping, attenuated interactions between pairs of ramping neurons, and dampened low-frequency oscillations. ConclusionsThese findings suggest that amphetamine alters prefrontal temporal processing by increasing the variability of prefrontal ramping. Our work provides insight into how amphetamine affects timing-related brain activity, which may be useful in developing new neurophysiological markers for amphetamine use and novel treatments targeting the prefrontal cortex.

neuroscience↗

bioRxiv2023

Complementary cognitive roles for D2-MSNs and D1-MSNs in interval timing

The role of striatal pathways in cognitive processing is unclear. We studied dorsomedial striatal cognitive processing during interval timing, an elementary cognitive task that requires mice to estimate intervals of several seconds and involves working memory for temporal rules as well as attention to the passage of time. We harnessed optogenetic tagging to record from striatal D2- dopamine receptor-expressing medium spiny neurons (D2-MSNs) in the indirect pathway and from D1-dopamine receptor-expressing MSNs (D1-MSNs) in the direct pathway. We found that D2-MSNs and D1-MSNs exhibited distinct dynamics over temporal intervals as quantified by principal component analyses and trial-by-trial generalized linear models. MSN recordings helped construct and constrain a four-parameter drift-diffusion computational model in which MSN ensemble activity represented the accumulation of temporal evidence. This model predicted that disrupting either D2-MSNs or D1-MSNs would increase interval timing response times and alter MSN firing. In line with this prediction, we found that optogenetic inhibition or pharmacological disruption of either D2-MSNs or D1-MSNs increased interval timing response times. Pharmacologically disrupting D2-MSNs or D1-MSNs also changed MSN dynamics and degraded trial-by-trial temporal decoding. Together, our findings demonstrate that D2-MSNs and D1-MSNs had opposing dynamics yet played complementary cognitive roles, implying that striatal direct and indirect pathways work together to shape temporal control of action. These data provide novel insight into basal ganglia cognitive operations beyond movement and have implications for human striatal diseases and therapies targeting striatal pathways.

neuroscience↗

bioRxiv2021

Spatio-temporal analysis identifies hotspots of marine mammal strandings along the Indian coastline: implications for developing a National Marine Mammal Stranding Response and Management policy

Marine mammal strandings provide vital information on their life histories, population health and status of marine ecosystems. Opportunistic reporting of strandings serve as a potent low-cost tool for conservation monitoring of these highly mobile species. We present the results of spatio-temporal analyses of marine mammal stranding events to identify hotpots along Indian coastline. We collated data over a long-time frame (~270 years) available from various open access databases, reports and publications. Given the inadequacy in data collection over these years, we grouped data into four major groups viz. baleen whales, toothed whales, small cetaceans and dugongs. Further, we described the trends in data for marine mammal sightings, incidental mortalities, induced mortalities and stranding events using the last group for spatio-temporal analysis. Annual strandings along the Indian coast has increased considerably in the recent years (11.25 {+/-} 9.10 strandings/ year), peaking in the last two years (2015-17, mean = 27.66{+/-}12.03 strandings /year). We found that number of strandings spiked in June- September along the west coast and December- January along the east coast. We identified several sections of coastline which have consistently received comparatively higher number of stranded animals (0.38 - 1.82 strandings/km) throughout the study period. Use of novel geospatial tool Emerging Hotspot Analysis revealed new and consecutive hotspots along the north-west coast, and sporadic hotspots along the south-east coast. Despite the challenges of working with an opportunistic database, this study highlights critical areas to be prioritized for monitoring marine mammal strandings in the country. We recommend establishing regional marine mammal stranding response centres at the identified hotspots coordinated by a National Stranding Monitoring Centre with adequate funding support. Regular conduct of stranding response programs for field veterinarians, frontline personnel focused around identified stranding hotspots would help develop a comprehensive picture of marine mammal populations in Indian waters.

ecology↗

bioRxiv2021

Legacy of draught cattle breeds of South India: Insights into population structure, genetic admixture and maternal origin

The present study is the first comprehensive report on diversity, population structure, genetic admixture and mitochondrial DNA variation in South Indian draught type zebu cattle. The diversity of South Indian cattle was moderately higher. A significantly strong negative correlation coefficient of -0.674 (P<0.05) was observed between the effective population size of different breeds and their estimated FIS. The phylogeny and genetic structure analysis revealed the distinctness of Kangayam, Vechur and Punganur cattle from the rest of the zebu breeds. The results showed the influence of Hallikar breed in the development of most Mysore type cattle breeds of South India with the exception of Kangayam. Bayesian clustering analysis was performed to assess the taurine admixture in South Indian zebu cattle using purebred Jersey and Holstein-Friesian as reference genotypes. Relatively high levels of taurine admixture (>6.25%) was observed in Punganur, Vechur, Umblachery and Pulikulam cattle breeds. Two major maternal haplogroups, I1 and I2, typical of zebu cattle were observed, with the former being predominant than the later. The pairwise differences among the I2 haplotypes of South Indian cattle were relatively higher than West Indian (Indus valley site) zebu cattle. The results indicated the need for additional sampling and comprehensive analysis of mtDNA control region variations to unravel the probable location of origin and domestication of I2 zebu lineage. The present study also revealed major concerns on South Indian zebu cattle (i) risk of endangerment due to small effective population size and high rate of inbreeding (ii) lack of sufficient purebred zebu bulls for breeding and (iii) increasing level of taurine admixture in zebu cattle. Availability of purebred semen for artificial insemination, incorporation of genomic/molecular information to identify purebred animals and increased awareness among farmers will help to maintain breed purity, conserve and improve these important draught cattle germplasms of South India.

genetics↗

bioRxiv2019

Mitochondrial phylogeography reveals high diversity and unique divergent lineage in Indian Dugongs (Dugong dugon)

O_LIIndia plays a central role in dugong conservation by hosting the largest population within south Asia. Current knowledge on status of Indian dugongs is limited due to paucity of reliable ecological data. This study generates mitochondrial control region sequences from about 10% of dugong population from major dugong populations within India. These data was compared with the global data to assess genetic lineages, population structure and genetic diversity of Indian populations. C_LIO_LIMultiple analyses suggest that the Indian dugong populations are part of a single genetic cluster, comprising south Asia, northwest Indian ocean and southwest Indian ocean populations. Despite small population size, they retain high genetic diversity with unique mitochondrial DNA haplotypes within south Asia. C_LIO_LIWithin India, novel haplotypes were observed from all sampling sites with overall high haplotype diversity (0.85{+/-}0.04) but low nucleotide diversity (0.005{+/-}0.001). Indian populations exhibit high genetic differentiation with higher within-population variance (63.41%) than among populations (36.59%), signaling population structure. Few haplotypes were shared with Sri Lanka and southeast Asian populations, indicating potential genetic connectivity. C_LIO_LIBeing the most genetically unique population within south Asia, Indian dugong populations are globally significant. We recommend that Indian Dugong populations should be managed as a Conservation Unit to ensure population recovery and long-term survival of the species. C_LI

molecular biology↗

bioRxiv2017

Standardizing microsatellite panels for individual identification of seabirds’ Snow Petrel Pagodroma nivea and Wilson’s Storm Petrel Oceanites oceanicus in Antarctica

Seabirds are known to be important indicators of marine ecosystems health. Procellariiformes are one of the most abundant seabird species distributed from warm tropical to cold temperate regions including Antarctica. With few long-term studies on breeding seabirds at the Antarctic continent, crucial biological parameters such as genetic variation, population genetic structure and past population demography is lacking for most of the commonly occurring species. Under the Biology and Environmental Sciences component of the Indian Antarctic programme, long-term monitoring of Antarctic biodiversity is being conducted. In this paper, we describe a panel of 12 and 10 cross-species microsatellite markers for two relatively less studied seabird species in Antarctica, snow petrel Pagodroma nivea and Wilsons storm petrel Oceanites oceanicus, respectively. These loci showed high amplification success and moderate level of polymorphism in snow petrel (mean no. of alleles 7.08{+/-}3.01 and mean observed heterozygosity 0.35{+/-}0.23), but low polymorphism in Wilsons storm petrel (mean no. of alleles 3.9{+/-}1.3 and mean observed heterozygosity 0.28{+/-}0.18). The results demonstrate that these panels can unambiguously identify individuals of both species from various types of biological materials. This work forms a baseline for undertaking long-term genetic research of Antarctic seabird species and provides critical insights into their population genetics.

genetics↗